Photic Regulation of Circadian Rhythms

描述（由申请人提供）：失明对患者的独立性和生产力的影响是深远的。虽然视力丧失是罪魁祸首，但伴随的非视觉光生理调节缺陷也显著导致生活质量下降。例如，由于昼夜生理无法与天文日光同步而导致的睡眠：觉醒周期失调可能会产生严重有害的社会后果。在过去的6年里，在识别视网膜感光器类别方面取得了巨大进展，这些感光器类别负责将昼夜生理与光：暗周期同步。在这些光感受器中，有一类新发现的内在光敏视网膜神经节细胞（ipRGCs）需要光色素黑视素对光敏感。视光感受器（视杆细胞和视锥细胞）也参与昼夜节律系统的调节。视觉光感受器和含有黑视素的ipRGCs将信息从眼睛传递到大脑的信号机制尚不清楚，也是本提案的主题。该提案的中心假设是ipRGCs和经典视觉光感受器相互作用，以光调节昼夜节律和其他形式的非视觉光生理。本提案的目的是了解这两个感光系统之间相互作用的本质。我们的基本原理是，增加对这些感觉模式及其相互作用的理解，将提供光疗策略和药理学切入点，以治疗诸如盲人复发性失眠和基于昼夜节律的睡眠障碍等疾病。

DESCRIPTION (provided by applicant): The effects of blindness on the independence and productivity of afflicted individuals are profound. Although the loss of vision is the primary culprit, concomitant deficits in the regulation of non-visual photophysiology also contribute significantly to the decrease in quality of life. For example, the dysregulation of the sleep:wake cycle because of an inability to photosynchronize circadian physiology with astronomical day can have severely detrimental social consequences. Within the last 6 years, great advances have been made in identifying the retinal photoreceptor classes responsible for synchronizing circadian physiology with the light:dark cycle. Among these photoreceptors is a newly discovered class of intrinsically photosensitive retinal ganglion cell (ipRGCs) that requires the photopigment melanopsin to be sensitive to light. The visual photoreceptors (the rods and cones) also contribute to the regulation of the circadian system. The signaling mechanisms by which the visual photoreceptors and the melanopsin-containing ipRGCs convey information from the eyes to the brain are yet to be understood and are the subject of this proposal. The central hypothesis of this proposal is that ipRGCs and the classical visual photoreceptors interact to photically regulate circadian rhythms and other forms of non-visual photophysiology. The purpose of this proposal is to understand the nature of this interaction between these 2 photoreceptive systems. Our rationale is that an increased understanding of these sensory modalities and their interactions will provide phototherpeutic strategies and pharmacologic entry points to treat maladies such as recurrent insomnia in the blind and circadian-based sleep disorders.